Several years ago, neonatal and adult rhesus monkeys were inoculated intravenously or orally with a live attenuated mutant of SIV, termed SIV(3. Long-term follow-up has revealed that this mutant has retained its ability to cause AIDS in infant and adult hosts. Of a total of 8 infant macaques vaccinated as neonates, 6 have died of AIDS, and the remaining 2 survivors exhibit signs of disease progression. Of 16 adult vaccine recipients, 6 had recurrence of chronic viremia associated also with persistent inversion of the CD4/CD8 ratios. Of these animals, 2 have died, one of uterine carcinoma and progressive SIV disease, the second one of end-stage AIDS. When we compared the median survival time of infants inoculated at birth with wild-type, nef+ SIVmac251 with that of SIV(3 vaccine recipients, a 3.8-fold prolongation of a median survival was noted in the vaccinees as compared to infants infected with wild-type virus. The residual pathogenicity of the multiply dele ted SIV(3 raises serious safety issues regarding the use of similarly attenuated HIV strains as human AIDS vaccine candidates. FUNDING NIH / NIAID $188,617 4/01/98 - 3/31/01 PUBLICATIONS Baba, T.W., Liska, V., Khimani, A.H., Ray, N.B., Dailey, P.J., Penninck, D., Bronson, R., Greene, M.F., McClure, H.M., Martin, L.N. and Ruprecht, R.M. Live attenuated multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques. Nat Med 5:194-203, 1999. Ruprecht, R.M., Baba, T.W., Liska, V., Ray, N.B., Martin, L.N., Murphy-Corb, M., Rizvi, T.A., Bernacky, B.J., Keeling, M.E., McClure, H.M. and Anderson, J. Oral transmission of primate lentiviruses. J Infect Dis (In press). P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center